Download Genes, Proteins, and proteins sill

HASPI Medical Biology Lab 02
Background/Introduction
Before humans even knew of the existence of DNA, they recognized
that certain traits were inherited. Through observation they saw that
plants and animals raised as food sources often took after their
parents. For example, the offspring of cows that produced large
amounts of milk or plants that produced a lot of fruit often produced
large amounts of milk or fruit themselves. This led to selective breeding
and recordings of the practice have been found from more than
2,000 years ago, while the existence of DNA was not discovered until
the mid-20th century.
http://www.abdn.ac.uk/news/images/Krista-cow_rdax_400x600.jpg
Through biological and engineering advances we now have a much greater understanding of the
structure and function of complex microscopic molecules such as DNA and protein. Scientific
experiments, simulations, microscopic observations, and computer models of DNA, genes, and proteins
have led to amazing breakthroughs in understanding how our bodies function. As a result, our
comprehension of diseases related to genes and proteins has and will continue to improve as well.
Genes, Chromosomes, and Proteins
Fast-forward 2,000 years and we now know that more than 100,000 proteins function in the human
body. Proteins can perform chemical reactions, contract to allow movement, act as hormones, make
up cell and body structures, store molecules, or transport molecules as a few examples of their function.
Proteins are created by the body, and require a set of directions. These directions are stored in
deoxyribonucleic acid or DNA. Every one of the trillions of cells in the human body has a complete set
of DNA stored in its nucleus. This means that every single cell in your body holds the directions to make
you!
A set of instructions in DNA that is used to make a specific protein is
called a gene. The instructions are written in a code using four different
nucleotide bases – adenine (A), thymine (T), cytosine (C), and guanine
(G). The order of these bases determines the order of amino acids,
which build proteins. There are 20 different amino acids and their order
determines the structure of the protein the gene creates. The structure
of DNA determines the structure of proteins, which carry out essential
functions of life through systems of specialized cells.
Where do chromosomes fit into all of this? The structure of DNA is called
a double helix. It is a long, twisted strand of about 3.2 billion nucleotide
pairs in humans. If DNA was not organized, it would be a mess. Imagine
having all of the 35,000 pages of an encyclopedia set (think Wikipedia
in books) ripped out and scattered on the floor. Now find the single
page on San Diego. Wouldn’t it make more sense to organize the
pages to make it easier to find? That’s why there are chromosomes!
Chromosomes are simply portions of DNA wound up and
organized into a form that makes it easier for cells to find
http://publications.nigms.nih.gov/insidelifescience/images/dna-structure.jpg
the directions, or gene, that it needs to make a specific
protein. Different organisms have a different number of
chromosomes depending on the amount of DNA, or
instructions, needed to build and keep that organism
functioning. Humans normally have two sets of 23
chromosomes. One set comes from each parent with the
same genes, but with different versions of those genes.
If they are the same, why do we have two sets?
Although each chromosome has the same genes that
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contain the directions for the corresponding protein, these genes can vary slightly and create the
differences we see among humans. For example, the gene for eye color that a child may inherit could
be blue, brown, green, or hazel. You will learn more about chromosome structure and inheritance in a
later activity.
From DNA to Protein
Now that you understand that DNA contains the code
for proteins, the question becomes how the code in
DNA actually leads to proteins? This process is incredibly
complex, but can be summarized in three steps:
transcription, protein synthesis or translation, and protein
folding.
Transcription
DNA is very fragile and it is vital that not be damaged.
For this reason, our bodies have created a way to make
a copy of DNA, specifically a gene, so that it doesn’t
have to leave the protection of the nucleus. The copy is
made out of RNA, or ribonucleic acid, called messenger
RNA, or mRNA. This copying process is called
transcription and ONLY occurs in the nucleus.
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Protein Synthesis or Translation
Once an mRNA copy of the gene has been created,
the ribosome can build a protein using the mRNA copy
as directions. The ribosome translates the order of
amino acids in the protein and bonds them together
into a chain.
Protein Folding
The length of the amino acid chain produced by ribosomes can range from only a few hundred to
hundreds of thousands of amino acids long. The amino acid chain is transported to the endoplasmic
reticulum (ER) where they are folded and can even have carbohydrates or lipids added to them to
produce functioning proteins. An amino acid chain cannot perform a function until it has been folded
into its functional shape.
Amino acid chains are also known as polypeptide chains. The
interactions and bonds that occur between the different amino acids
are what cause the folding and shaping of the protein. Every amino
acid has a functional side that can cause or prohibit bonding with
other amino acids. Proteins, called chaperones, can assist an amino
acid chain during the folding and bonding process to create a
finished protein that can now perform a function in the body.
Mutations
Even though our body has developed mechanisms to protect DNA,
http://www.interactive-biology.com/wpcontent/uploads/2012/05/Human-Insulinit can still become damaged. A mutation can occur when DNA is
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not copied correctly or affected by external influences. When a mutation occurs in DNA it can alter the
gene, and therefore the order of amino acids. This can change the function of the protein. The best
way to demonstrate the impact of a mutation on a protein is to compare it to a sentence. Similar to
words in a sentence, the DNA sequence determines the order of amino acids in a protein. Think of a
gene as a sentence made up of three-letter words (codons) and each letter is a DNA nucleotide. The
DNA sequence might look like this:
Momanddadaresadthepigwasnotfat.
Split into sets of three nucleotides called codons it would read like this:
Mom and dad are sad the pig was not fat.
What if a single letter (DNA nucleotide) was left out? For example, if we remove the third letter of the
sentence we get:
Moa ndd ada res adt hep igw asn otf at.
Notice that a single mistake creates a sentence (gene) that no longer makes sense. This is what
happens when a mutation occurs within the DNA sequence. Table 1 shows some
common mutations.
Table 1. Different Types of Mutations
Normal
Nonsense
Insertion
Missense
Deletion
Silent
http://academic.pgcc.edu/~kroberts/Lecture/Chapter%207/07-21_PointMutations_L.jpg
Cystic Fibrosis
Cystic fibrosis is a common genetic disease caused by a
mutation in a gene called the cystic fibrosis transmembrane
conductance regulator (CFTR) gene. The CFTR gene is located
on chromosome 7 and has the directions to create the CFTR
protein. The CFTR protein is a channel protein that regulates
how salts, most commonly sodium (Na+) and chloride (Cl-),
and water move through the cell membranes of epithelial
cells. Epithelial cells cover surfaces of the body and can be
found in the skin, respiratory, and digestive tracts.
http://www.personal.psu.edu/users/j/n/jnb5091/Images/CFTR%20Protein.jpg
Na+ and Cl- help control the movement of water into tissues. When the CFTR protein does not function
correctly, chloride (Cl-) is unable to pass through the center channel and sodium (Na+) is also unable to
pass through he cell membrane. When they are imbalanced, watery substances like mucus are unable
to move into the tissues and the mucus becomes extremely sticky and thick. (The role of mucus is to
lubricate the surfaces of the body.) As a result, symptoms of cystic fibrosis include:
 Extremely salty skin
 Thick, sticky mucus that can block respiratory and digestive tracts
 Frequent respiratory infections due to bacteria trapped in mucus
 Wheezing, persistent cough, and shortness of breath
 Lack of digestion leading to poor growth/weight
The cystic fibrosis mutation is a recessive disorder passed from parent to offspring. This means an
individual needs two copies of the mutated CFTR gene to have cystic fibrosis. Since the
mutation is recessive, a parent may not have symptoms of cystic fibrosis or know they carry the
mutation. There are more than 30,000 people in the U.S. with cystic fibrosis and more than 1,000 cases
are diagnosed yearly. More than 10 million people in the U.S. are carriers of cystic fibrosis. When cystic
fibrosis was first discovered, few sufferers lived past 6 years old, but due to medical advances the
median age of survival has increased to 37 years old.
Review Questions – answer questions on a separate sheet of paper
1. What are proteins? Give 3 examples of functions they perform.
2. How are DNA, genes, chromosomes, and proteins related?
3. What are amino acids? Explain how they determine the structure of protein.
4. How many chromosomes do humans have? Why do humans have two sets of chromosomes?
5. Describe transcription. Why is it important for DNA to remain in the nucleus?
6. Describe translation.
7. Describe protein folding. What causes an amino acid chain to fold?
8. What is a mutation? Explain how a mutation in a gene can influence the protein it creates.
9. List and explain 3 types of mutations.
10. What is cystic fibrosis? List 3 symptoms associated with cystic fibrosis.
11. What is the purpose of the CFTR protein?
12. What happens when the CFTR protein is mutated?
13. How does an individual get cystic fibrosis?
14. If a mother is a carrier, and the father is normal, what are the chances their children will have
cystic fibrosis?